The invention relates to a method of contrast enhanced magnetic resonance imaging (MRI), and in particular to the use of magnetic particles as diagnostic contrast agents in MRI.
In diagnostic medicine, contrast agents are today being used primarily in X-ray diagnostics whore an increased contrast effect is obtained during examination of, for example, internal organs, such as the kidneys, the urinary tract, the digestive tract, the vascular system of the heart (angiography), etc. This contrast effect is based upon the fact that the contrast agent itself is less permeable to X-rays than the surrounding tissue, as a result of which a different blackening of the X-ray plate is obtained.
X-raying implies certain radiation hazards, but during angiography the complication risk is associated in particular with the use of contrast agents.
In recent years, a number of now methods have been introduced in diagnostic radiology. One such method goes by the name NMR (Nuclear Magnetic Resonance) which provides information not only about the distribution of the water content in a specific tissue (in contradistinction to radiology which merely gives a measure of the transmissibility of the X-rays in a specific tissue), but also about the chemical tissue structure which is different in normal and pathological tissue.
In the NMR method, a strong and homogeneous magnetic field is applied across the tissue to be examined. By studying the so-called relaxation times of the protons of the molecules present, especially the protons of the water, it is possible to produced via comprehensive and complex computer calculations, a visual image of the structure of the tissue concerned. (This technique is now commonly referred to as magnetic resonance imaging or MRI).
There is, however, an interest in being able to make a differential diagnosis between pieces of tissue having a high density of blood vessels and, alternatively, tissue having a low density of vessels. Such a situation which has considerable clinical interest, comprises the localisation of tumours which, in their periphery, have a higher density of vessels as compared with normal tissue.
One useful method in this context is to inject into the vascular system particles responsive to a magnetic field and showing changes in the above-mentioned relaxation times.
By "magnetic particles" or "magnetically responsive particles" as used herein is meant particles of materials, such as magnetite, which have a Curie temperature and thus are ferromagnetic, ferrimagnetic or, at sub-domain size, superparamagnetic. Superparamagnetic particles exhibit the cooperative magnetic effects of ferri- or ferromagnetism when exposed to magnetic fields but, being sub-domain size, lose their magnetization in the absence of the field. Magnetite particles of 10-20 nm size for example are superparamagnetic.
These magnetic particles interfere with the above-mentioned homogeneous magnetic field in that there is formed, around each individual particle, a field gradient which in its turn changes the relaxation times of nearby protons causing a fall-off in MR signal intensity. Put more simply, this means that "black holes" are formed around each particle which may be visualized and thus give an impression of the vessel density in the tissue in question.